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Serum p97 levels as an aid to identifying Alzheimer's disease
H. Feldman1, R. Gabathuler, M. Kennard
1Division of Neurology, University of British Columbia, Clinic for Alzheimer's Disease and Related Disorders, Vancouver, Canada.
Abstract:
Background: The application of formal clinical diagnostic criteria for the identification of Alzheimer's Disease (AD) has improved diagnostic sensitivity. However, there remains a need for non-invasive biological markers and laboratory tests, which can facilitate case identification, and the assessment of treatment response. The p97 protein is a secreted protein specifically expressed by amyloid plaque associated reactive microglia that may have AD diagnostic ability. Methods: A quantitative radioimmunoassay was developed to measure serum p97. This study, under a double blind protocol, evaluated the utility of serum p97 as diagnostic test for AD. All subjects were referred to the UBC Clinic for Alzheimer's Disease and Related Disorders (CADRD) for clinical assessment of dementia. A serum p97 sample was obtained at the time of assessment but diagnosis of disease was determined independently of p97 examination. Results: "Possible" and "probable" AD cases (n = 41) and cognitively normal controls (n = 64) showed a highly significant difference in mean p97 concentration (41 vs. 20 ng/ml, p<0.001). There was some overlap in p97 distributions between AD cases and control subjects. The area under the curve (AUC) for the receiver operator curve (ROC) was 0.812. Conclusions: These results further support the specificity of high serum p97 levels in AD and its potential utility as a biological marker in AD. The reproducible elevation of serum p97 in AD underlines the need to further determine its role as a biological marker and diagnostic adjunct for AD.
Insights
Serum p97 protein levels are significantly higher in Alzheimer's Disease (AD) patients compared to healthy individuals. This finding supports p97's potential as a novel biomarker for AD diagnosis.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Diagnostics
Background:
- Formal clinical criteria improve Alzheimer's Disease (AD) diagnosis sensitivity.
- Non-invasive biomarkers are needed for AD case identification and treatment monitoring.
- The p97 protein, secreted by microglia near amyloid plaques, shows potential as an AD biomarker.
Purpose of the Study:
- To evaluate the diagnostic utility of serum p97 levels as a non-invasive biomarker for Alzheimer's Disease (AD).
- To assess the correlation between serum p97 concentration and AD diagnosis.
Main Methods:
- Developed a quantitative radioimmunoassay to measure serum p97 levels.
- Conducted a double-blind study comparing serum p97 in AD patients and cognitively normal controls.
- Clinical diagnoses were determined independently of p97 measurements.
Main Results:
- Significantly higher mean serum p97 concentrations were observed in "possible" and "probable" AD cases (41 ng/ml) versus controls (20 ng/ml) (p<0.001).
- Receiver operator curve analysis yielded an area under the curve (AUC) of 0.812, indicating good diagnostic performance.
- Some overlap in p97 distributions between AD and control groups was noted.
Conclusions:
- Elevated serum p97 levels are specific to Alzheimer's Disease (AD).
- Serum p97 demonstrates potential as a valuable biological marker and diagnostic adjunct for AD.
- Further research is warranted to fully elucidate the role of p97 in AD diagnostics.